羟基磷灰石作为吸收剂的研究

发布时间：2019-03-04 12:56

【摘要】：如果主药为油性药物或主药含挥发油成分时，此时常常加入一定量的吸收剂以便于压片成型，提高药物压片成型性。吸收剂的用量往往由药物中油性成分的含量决定，通常吸收剂用量占处方总量的10%。药典收载的常见吸收剂对油性成分的容纳量一般都不大，通常吸收剂的用量占到油性成分含量的三倍甚至更多，对油性药物特别是主药含量大的油性药物的片重会有较大影响，增加病人服用药物片数，降低了患者对药物的顺应性，不利于药物的市场发展。因此，新型高效的吸收剂的开发对油性药物片剂的制备是必不可少的一项工作。羟基磷灰石（Hydroxyapatite，HAP，Ca10（PO4）6(OH)2)是牙齿和骨骼的主要无机矿物成分，安全无毒，生物相容性高。羟基磷灰石同时系属多孔性物质，能够吸附吸收油性药物，使油性药物进入羟基磷灰石的孔道中，较药典收载的一般的吸收剂相比，，羟基磷灰石对油性药物的吸收容纳性更强，容纳量更高。目前，尚未有文献报道羟基磷灰石在药物吸收剂方面的应用研究。本文以液体油性药物维生素E为模型药物，研究了羟基磷灰石对油性药物的吸收容纳量及吸收剂性能的影响因素，并以羟基磷灰石为吸收剂制备了维生素E片，同时研究了维生素E片的质量标准。实验结果表明：羟基磷灰石克服了药典收载的常规吸收剂的容纳量小的问题，其对油性药物维生素E的吸收容纳量比磷酸氢钙高3.4倍、比碳酸钙高2.6倍、比硫酸钙高2.47倍。比表面积和孔容则可能是影响物质吸收性能的因素。羟基磷灰石用作维生素E片的吸收剂时，制粒过程中容易过筛，压制时不粘冲不裂片，压出的片剂外观光洁，颜色均匀，无色差，硬度大，片重差异小且符合药典片重差异限度，药片含量均一度也在药典规定范围值内。与磷酸氢钙、碳酸钙和硫酸钙等药典收载的吸收剂相比，羟基磷灰石能更好解决因油性组分存在而引起聚合力差，颗粒松散易碎、颗粒流动性不良，易松片裂片、易粘冲，片子硬度过小、片重差异过大等问题。此外，研究还发现羟基磷灰石还能增加维生素E片的稳定性，加速试验中，羟基磷灰石为吸收剂的维生素E片的保存期比磷酸氢钙、硫酸钙和碳酸钙为吸收剂的维生素E片的保存期延长了1个月，长期试验中羟基磷灰石为吸收剂的维生素E片的保存期比磷酸氢钙、硫酸钙和碳酸钙为吸收剂的维生素E片的保存期延长了3个月。综上：羟基磷灰石有望成为新型药用辅料，为挥发油及油性药物提供了一种高效的吸收剂，为吸收剂家族添加了一个新成员，同时扩展了羟基磷灰石的应用范围，增加了羟基磷灰石的实用性。
[Abstract]:If the main drug is an oily drug or the main drug contains volatile oil components, at this time a certain amount of absorbent is often added in order to facilitate the molding of the tablet and improve the formability of the drug tablet. The dosage of the absorbent is usually determined by the content of the oil component in the drug, which usually accounts for 10% of the total prescription. The common absorbents contained in pharmacopoeia generally have little capacity for oil components, usually the amount of absorbents accounts for three times or more of the oil components, and it will have a great impact on the weight of oily drugs, especially those with large contents of main drugs. Increasing the number of drug tablets, reducing the patient's compliance to drugs, is not conducive to the development of the drug market. Therefore, the development of new and efficient absorbents is necessary for the preparation of oily drug tablets. Hydroxyapatite (Hydroxyapatite,HAP,Ca10 (PO4) 6 (OH) 2) is the main inorganic mineral component of teeth and bones. It is safe and non toxic and has high biocompatibility. Hydroxyapatite is also a porous substance, which can adsorb and absorb oil drugs, and make oil drugs into the pores of hydroxyapatite. Compared with the general absorbents contained in Pharmacopoeia, the absorption capacity of hydroxyapatite to oil drugs is stronger than that of the general absorbents contained in Pharmacopoeia. The capacity is higher. At present, the application of hydroxyapatite in drug absorbents has not been reported in literature. In this paper, vitamin E, a liquid oil drug, was used as the model drug to study the influence factors of hydroxyapatite on the absorption capacity and absorbent performance of the oil drug, and the vitamin E tablets were prepared by using hydroxyapatite as the absorbent. At the same time, the quality standard of vitamin E tablets was studied. The results show that hydroxyapatite overcomes the problem of low capacity of conventional absorbents contained in Pharmacopoeia, and its absorption capacity to oil drug vitamin E is 3.4 times higher than that of calcium hydrogen phosphate and 2.6 times higher than that of calcium carbonate, and the absorption capacity of hydroxyapatite is 3.4 times higher than that of calcium hydrogen phosphate and 2.6 times higher than calcium carbonate. It is 2.47 times higher than calcium sulfate. The specific surface area and pore volume may be the factors affecting the absorption performance of the material. When hydroxyapatite is used as absorbent of vitamin E tablets, it is easy to sift in the granulation process, does not stick to impingement and does not crack when pressing, and the tablet has a smooth appearance, uniform color, no color difference and high hardness, and has the advantages of smooth appearance, uniform color and high hardness. The difference of tablet weight is small and accords with the limit of weight difference of Pharmacopoeia tablets, and the contents of tablets are also within the prescribed range of Pharmacopoeia. Compared with the absorbents contained in pharmacopoeia, such as calcium hydrogen phosphate, calcium carbonate and calcium sulfate, hydroxyapatite can better solve the problem of poor coalescence due to the presence of oil components, loose and fragile particles, poor fluidity of particles, easy loosening of fragments, and easy adhesion and erosion. The hardness of the film is too small, and the difference in the weight of the film is too big and so on. In addition, the study also found that hydroxyapatite can also increase the stability of vitamin E tablets, accelerated the test, hydroxyapatite as absorbent vitamin E tablets storage life than calcium hydrogen phosphate, The shelf life of vitamin E tablets with calcium sulfate and calcium carbonate as absorbents was extended by one month. In the long-term test, the retention period of vitamin E tablets with hydroxyapatite as absorbent was higher than that of calcium hydrogen phosphate. The shelf life of vitamin E tablets with calcium sulfate and calcium carbonate as absorbers was extended by 3 months. Above all: hydroxyapatite is expected to become a new type of medicinal adjunct, providing an efficient absorbent for volatile oil and oily drugs, adding a new member to the absorbent family, and expanding the scope of application of hydroxyapatite at the same time. It increases the practicability of hydroxyapatite.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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